Positive 144-week data have been reported from two phase 3 studies of Genvoya (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, Gilead Sciences) for the treatment of human immunodeficiency virus-1 (HIV-1) infection in treatment-naïve adults. Through week 144, Genvoya demonstrated significantly higher rates of virologic suppression compared with Stribild (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg, Gilead), based on the percentage of patients with HIV-1 RNA levels of less than 50 copies/mL.
Genvoya is indicated for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (i.e., HIV-1 RNA levels of less than 50 copies/mL) on a stable antiretroviral regimen for at least six months, with no history of treatment failure and no known resistance to the components of Genvoya. The label for Genvoya includes a boxed warning regarding the risk of lactic acidosis/severe hepatomegaly with steatosis, and the risk of post-treatment acute exacerbation of hepatitis B.
Studies 104 and 111, originally planned for 96 weeks and extended to 144 weeks, were randomized, double-blind, controlled trials involving a total of 1,733 treatment-naïve adults with HIV-1 infection.
At week 144, 84% (729/866) of patients treated with Genvoya and 80% (694/867; P = 0.021) of patients treated with Stribild achieved HIV-1 RNA levels of less than 50 copies/mL. In addition, at week 144, 81% (702/866) of the Genvoya group and 76% (657/867; P = 0.006) of the Stribild group had HIV-1 RNA levels of less than 20 copies/mL, a secondary endpoint. At week 144, virologic failure was similar between the two groups (Genvoya, 4.6%, vs. Stribild, 3.9%). There were significantly fewer adverse events leading to discontinuation in the Genvoya arm compared with the Stribild arm (1.3% vs. 3.3%, respectively; P = 0.01). In both groups, the most common drug-related adverse events included nausea, diarrhea, and headache.
A separate analysis investigated the effect of the two regimens on laboratory parameters of kidney, bone, and plasma lipid levels. To examine kidney function, specific protein markers of glomerular and tubular function were examined, all of which favored Genvoya. This included a statistically significant difference in the median change in the estimated glomerular filtration rate from baseline to week 144 (Genvoya, –1.6 mL/min, vs. Stribild, –7.7 mL/min; P < 0.001). No subjects receiving Genvoya had renal-related discontinuations compared with 12 subjects in the Stribild arm (P ˂ 0.001). The analysis also found that reductions in bone mineral density were significantly less in the Genvoya group compared with the Stribild group for both lumbar spine (Genvoya, –0.92%, vs. Stribild, –2.95%; P <0.001) and total hip (Genvoya, –0.75%, vs. Stribild, –3.36%; P < 0.001).
Patients treated with Genvoya had statistically greater increases in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol from baseline to week 144 compared with those treated with Stribild. There was no significant difference in the total cholesterol-to-HDL ratio at week 144 between the two groups.
Source: Gilead Sciences; February 14, 2017.